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Clinical and genetic features of cystic fibrosis in Japan

Journal of Human Genetics volume 68, pages 671–680 (2023)Cite this article

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Abstract

Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common hereditary disease in Caucasians, it is rare in East Asia. In the present study, we have examined clinical features and the spectrum of CFTR variants of CF patients in Japan. Clinical data of 132 CF patients were obtained from the national epidemiological survey since 1994 and CF registry. From 2007 to 2022, 46 patients with definite CF were analyzed for CFTR variants. All exons, their boundaries, and part of promoter region of CFTR were sequenced and the presence of large deletion and duplications were examined by multiplex ligation-dependent probe amplification. CF patients in Japan were found to have chronic sinopulmonary disease (85.6%), exocrine pancreatic insufficiency (66.7%), meconium ileus (35.6%), electrolyte imbalance (21.2%), CF-associated liver disease (14.4%), and CF-related diabetes (6.1%). The median survival age was 25.0 years. The mean BMI percentile was 30.3%ile in definite CF patients aged < 18 years whose CFTR genotypes were known. In 70 CF alleles of East Asia/Japan origin, CFTR-dele16-17a-17b was detected in 24 alleles, the other variants were novel or very rare, and no pathogenic variants were detected in 8 alleles. In 22 CF alleles of Europe origin, F508del was detected in 11 alleles. In summary, clinical phenotype of Japanese CF patients is similar to European patients, but the prognosis is worse. The spectrum of CFTR variants in Japanese CF alleles is entirely different from that in European CF alleles.

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Acknowledgements

We thank Drs. Ito S, Ichinoi N, Wada Y, Sakamoto O, Sanada Y, Harada Y, Shoji S, Hoshikawa Y, Kanda K, Kando N, Shimizu M, Ichihara T, Endo A, Mizuno Y, Obata M, Maruyama S, Baba Y, Yanagimoto K, Arai K, Kojima D, Sato Y, Itoh K, Takahara T, Harada T, Ishii H, Kushima H, Fukuda Y, Tanoue K, Kawakita R, Murakami Y, Asao T, Kitabayashi T, Azuma A, Usuki J, Koga H, Hagio Y, Fukasawa M, Fukaya S, Ito R, Abukawa D, Hoshi Y, Umetsu S, Ishii M, Kojiro M, Kawase M, Tabata K, Ito T, Arakaki Y, Yokoyama N, Mitani Y, Fukumori T, Ishikawa S, Wada T, Nagai Y, Shiona S, Sakata Y, Yamasaki K, Igata F, and Ishii H for providing clinical data of CF patients. We thank Dr. Stewart AK for English editing of the manuscript.

Funding

This work was supported by grants from the Japan Society for the Promotion of Science, the Japanese study group for pediatric rare and intractable hepato-biliary-pancreatic diseases provided by the Ministry of Health, Labour, and Welfare of Japan, and scholarship donations by Chugai Pharmaceutical Co. Ltd.

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Author notes

  1. Tomoya Fukuyasu

    Present address: Department of Food and Nutrition, Tsu City College, Tsu, Japan

Authors and Affiliations

  1. Department of Human Nutrition, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Yuka Kozawa, Akiko Yamamoto, Miyuki Nakakuki, Takuto Okada, Tomoya Fukuyasu, Makoto Yamaguchi, Itsuka Taniguchi, Nao Nomura, Libin Liu, Mayuko Higuchi, Erina Niwa & Hiroshi Ishiguro

  2. Department of Nutrition, Nagoya University of Arts and Sciences, Nisshin, Japan

    Kotoyo Fujiki

  3. Department of Health and Nutrition, Nagoya Women’s University, Nagoya, Japan

    Shiho Kondo

  4. Division of Molecular Therapy, Department of Pharmaceutical Sciences, School of Pharmacy and Center for Basic Medical Research, International University of Health and Welfare, Otawara, Japan

    Yoshiro Sohma

  5. Miyoshi Municipal Hospital, Miyoshi, Japan

    Satoru Naruse

  6. Department of Surgery, Kindai University School of Medicine, Osakasayama, Japan

    Yoshifumi Takeyama

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Kozawa, Y., Yamamoto, A., Nakakuki, M. et al. Clinical and genetic features of cystic fibrosis in Japan. J Hum Genet 68, 671–680 (2023). https://doi.org/10.1038/s10038-023-01160-2

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